UNIPROT #

P04629

PROTEIN NAME

TrkA

SYNONYMS

gp140trk antibody; High affinity nerve growth factor receptor antibody; High affinity nerve growth factor receptor precursor antibody; MTC antibody; Neurotrophic tyrosine kinase receptor type 1 antibody; NTRK1 antibody; NTRK1_HUMAN antibody; Oncogene TRK antibody; p14-TrkA antibody; p140 TrkA antibody; p140-TrkA antibody; Slow nerve growth antibody; Trk A antibody; TRK antibody; Trk-A antibody; TRK1 antibody; TRK1-transforming tyrosine kinase protein antibody; Tropomyosin-related kinase A antibody; Tyrosine kinase receptor A antibody; Tyrosine kinase receptor antibody

SEQUENCE SIMILARITIES

Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.

TISSUE SPECIFICITY

Isoform TrkA-I is found in most non-neuronal tissues. Isoform TrkA-II is primarily expressed in neuronal cells. TrkA-III is specifically expressed by pluripotent neural stem and neural crest progenitors.

POST-TRANSLATIONAL MODIFICATION

Ligand-mediated autophosphorylation. Interaction with SQSTM1 is phosphotyrosine-dependent. Autophosphorylation at Tyr-496 mediates interaction and phosphorylation of SHC1.; N-glycosylated. Isoform TrkA-I and isoform TrkA-II are N-glycosylated.; Ubiquitinated. Undergoes polyubiquitination upon activation; regulated by NGFR. Ubiquitination by NEDD4L leads to degradation. Ubiquitination regulates the internalization of the receptor (By similarity).

SUBCELLULAR LOCATION

Cell membrane, Early endosome membrane, Late endosome membrane.

FUNCTION

The family of Trk receptor tyrosine kinases consists of TrkA, TrkB, and TrkC. While the sequence of these family members is highly conserved, they are activated by different neurotrophins: TrkA by NGF, TrkB by BDNF or NT4, and TrkC by NT3. Neurotrophin signaling through these receptors regulates a number of physiological processes, such as cell survival, proliferation, neural development, and axon and dendrite growth and patterning. In the adult nervous system, the Trk receptors regulate synaptic strength and plasticity. TrkA regulates proliferation and is important for development and maturation of the nervous system. Point mutations, deletions, and chromosomal rearrangements (chimeras) cause ligand-independent receptor dimerization and activation of TrkA. TrkA is activated in many malignancies including breast, ovarian, prostate, and thyroid carcinomas. Research studies suggest that expression of TrkA in neuroblastomas may be a good prognostic marker as TrkA signals growth arrest and differentiation of cells originating from the neural crest.